Process for the preparation of cyclic enol ethers

ABSTRACT

The present invention relates to a process for the preparation of cyclic enol ethers.

CROSS-REFERENCE TO RELATED APPLICATIONS

This application claims benefit (under 35 USC 119(e)) of U.S.Provisional Application 61/502,879, filed Jun. 30, 2011, which isincorporated by reference.

The present invention relates to a process for the preparation of cyclicenol ethers.

Cyclic enol ethers are important intermediates in the synthesis ofmacrocyclic lactones, which are used as fragrances. For example, U.S.Pat. No. 3,890,353 describes the preparation of saturated15-pentadecanolide (Exaltolide®) of the formula (a),

where the cyclic enol ether13-oxa-1,12-didehydrobicyclo[10.4.0]hexadecane of the formula (b) servesas starting material.

In addition to the 16-ring lactones described above, 15-ring lactonesare also described as musk-like fragrances. For example, EP 0 862 911describes saturated and unsaturated 15-ring lactones of the formulae(d1) and (d2), where R is methyl or hydrogen.

MST/Ya Aug. 11, 2011 0 FIG./0 Seq

The 15-ring lactones can be prepared starting from the correspondingcyclic enol ether of the formula (e).

-   -   where R is H or Me

The preparation of cyclic enol ethers, which are suitable as fragrancesor for producing fragrances, is described, for example, in GB 1266092,DE 2136496, U.S. Pat. No. 3,890,353, DE 25 11 410, DE 29 06 296 or JP2010-95447.

In some cases, the starting materials for the preparation of the cyclicenol ethers are not easily accessible and/or the preparation of thecyclic enol ethers proceeds via multistage syntheses with at times pooryields, sometimes the reaction conditions for the cyclization are verydrastic, for example by virtue of using relatively large amounts ofconcentrated sulfuric acid, or the processing of the cyclic enol ethersis still not satisfactory from the point of view of cost, or largeexcesses of reagents or starting materials are required.

Proceeding from this prior art, the object was to find flexible and moreefficient synthesis routes to fragrances of this type.

This object is achieved by a process for the preparation of cyclic enolethers of the formulae (I) and/or (II)

by cyclization of a starting compound of the formula (III)

in which

-   m is zero (0), one (1) or two (2),-   R¹ is an organic radical with 1 to 20 carbon atoms,-   R² is hydrogen or an organic radical having 1 to 20 carbon atoms,    or the radicals R¹ and R², together with the atoms connecting them,    form a mono- or polycyclic, substituted or unsubstituted ring system    with 3 to 20 carbon atoms which can also comprise heteroatoms    selected from the group consisting of the elements Si, N, P, O, and    S,-   R³ is hydrogen or an organic radical with 1 to 20 carbon atoms,-   R⁴ is hydrogen or an organic radical with 1 to 20 carbon atoms, and-   R⁵ is hydrogen or an organic radical with 1 to 20 carbon atoms.    in the presence of a Brønsted acid or Lewis acid, where the reaction    is carried out as reactive distillation, where the formed cyclic    enol ethers of the formulae (I) and/or (II) are separated off from    the starting compound of the formula (III) by distillation from the    reaction mixture.

The Brønsted acids which can be used in the process according to theinvention are either organic or inorganic acids. Preference is given toBrønsted acids which themselves cannot react with the starting compoundof the formula (III), i.e. are not consumed in a reaction, but merelyserve as a proton source for a chemical reaction catalyzed by protons.Nonlimiting examples of particularly suitable Brønsted acids aresulfuric acid, phosphoric acid, methanesulfonic acid, p-toluenesulfonicacid, strong acidic ion exchangers, tetrafluoroboric acid,trifluoroacetic acid, formic acid or oxalic acid.

Lewis acids which can be used in the process according to the inventionare, for example, aluminum trichloride, tin tetrachloride, titaniumtetrachloride, zirconium tetrachloride, iron trichloride or nickeldichloride.

The amount of Brønsted acid or Lewis acid which is used in the processaccording to the invention can be varied within a wide range. Inprinciple, the molar ratio of the Brønsted acid or Lewis acid to thecompound of the formula (III) can be greater than, equal to or lessthan 1. In principle, traces of acid suffice to catalyze thecyclization.

Preferably, in the process according to the invention, the molar ratioof the Brønsted acid or Lewis acid, in particular of the Brønsted acid,to the compound of the formula (III) is not greater than 1, particularlypreferably not greater than 0.15, very particularly preferably between0.1 and 0.0005, in particular between 0.07 and 0.001.

Preferably, in the process according to the invention, the cyclizationis carried out in the presence of a Brønsted acid. Preference is givenhere to using Brønsted acids with a pKa value of less than 5,particularly preferably less than 2.5, in particular less than 0. Veryparticularly preferably, the pKa value of the Brønsted acid is between−1.5 and −11.

A reactive distillation is a chemical process known in principle to theperson skilled in the art in which a single-stage or multi-stagedistillation is connected with a chemical reaction, in the present casea cyclization. The reaction product, in the present case a cyclic enolether of the formulae (I) and/or (II), is separated off continuously bydistillation from the starting material, a ketone.

Preferably, the reactive distillation and/or the cyclization reaction iscarried out in a temperature range between 50° C. and 300° C.,particularly preferably between 80° C. and 200° C.

Depending on the boiling points of the compounds to be separated, theperson skilled in the art can usually ascertain, directly or after a fewexperiments, suitable measures with regard to the distillation columnswhich can be used, the required separation efficiency of such a column,and also the distillation parameters such as, for example, pressure,temperature and reflux ratio, and/or make a suitable selection in orderto be able to carry out the process according to the invention in thedesired manner.

Unless limited further, the substituents according to the presentinvention are defined as follows:

The term “organic radical with 1 to 20 carbon atoms”, as usedpreviously, refers, for example, to C₁-C₂₀-alkyl radicals, saturatedC₃-C₂₀-heterocyclic radicals, C₆-C₂₀-aryl radicals,C₂-C₂₀-hetero-aromatic radicals or C₇-C₂₀-arylalkyl radicals, where thecarbon-containing radical can comprise further heteroatoms selected fromthe group of the elements consisting of F, Cl, Br, I, N, P, Si, O and Sand/or can be substituted with functional groups.

The term “alkyl”, as used in the present case, includes linear and mono-and optionally also poly-branched saturated hydrocarbons, which may alsobe cyclic. Preference is given to a C₁-C₁₀-alkyl, such as methyl, ethyl,n-propyl, n-butyl, n-pentyl, n-hexyl, n-heptyl, n-octyl, n-nonyl,n-decyl, cyclopentyl, cyclohexyl, isopropyl, isobutyl, isopentyl,isohexyl, sec-butyl or tert-butyl.

The term “saturated heterocyclic radical”, as used previously, refers,for example, to mono- or polycyclic, substituted or unsubstitutedhydrocarbon radicals in which one or more hydro-carbons, CH groupsand/or CH₂ groups are replaced by heteroatoms, preferably selected fromthe group consisting of the elements O, S, N and P. Preferred examplesof substituted or unsubstituted saturated heterocyclic radicals arepyrrolidinyl, imidazolidinyl, pyrazolidinyl, piperidyl, piperazinyl,morpholinyl, tetrahydrofuranyl, tetrahydropyranyl, tetrahydrothiophenyland the like, and also derivatives thereof substituted with methyl,ethyl, propyl, isopropyl and tert-butyl radicals.

The term “aryl”, as used previously, refers, for example, to aromaticand optionally also condensed polyaromatic hydrocarbon radicals whichmay optionally be mono- or poly-substituted with linear or branchedC₁-C₁₀-alkyl, C₁-C₁₀-alkoxy, C₂-C₁₀-alkenyl or halogen, in particularfluorine. Preferred examples of substituted or unsubstituted arylradicals are in particular phenyl, fluorophenyl, 4-methylphenyl,4-ethylphenyl, 4-n-propylphenyl, 4-isopropyl-phenyl, 4-tert-butylphenyl,4-methoxyphenyl, 1-naphthyl, 9-anthryl, 9-phenanthryl,3,5-dimethyl-phenyl, 3,5-di-tert-butylphenyl or 4-trifluoromethylphenyl.

The term “heteroaromatic radical”, as used previously, refers, forexample, to aromatic hydrocarbons in which one or more carbon atoms arereplaced by nitrogen atoms, phosphorus atoms, oxygen atoms or sulfuratoms or combinations thereof. Like the aryl radicals, these can beoptionally mono- or polysubstituted with linear or branchedC₁-C₁₀-alkyl, C₁-C₁₀-alkoxy, C₂-C₁₀-alkenyl or halogen, in particularfluorine. Preferred examples are furyl, thienyl, pyrrolyl, pyridyl,pyrazolyl, imidazolyl, oxazolyl, thiazolyl, pyrimidinyl, pyrazinyl andthe like, and also derivatives thereof substituted with methyl, ethyl,propyl, isopropyl and tert-butyl radicals.

The term “arylalkyl”, as used previously, refers, for example, toaryl-containing substituents whose aryl radical is linked via an alkylchain to the corresponding radical of the molecule. Examples are benzyl,substituted benzyl, phenethyl, substituted phenethyl and the like.

The radical R¹ is an organic radical with 1 to 20 carbon atoms, such as,for example, C₁-C₂₀-alkyl, C₆-C₂₀-aryl, arylalkyl or alkylaryl with 1 to10, preferably 1 to 4, carbon atoms in the alkyl radical and 6 to 14,preferably 6 to 10, in particular 6, carbon atoms in the aryl radical, asaturated heterocyclic radical with 3 to 20 carbon atoms or aheteroaromatic radical with 3 to 20 carbon atoms having in each case atleast one heteroatom selected from the group consisting of the elementsN, P, O and S, in particular N, O and S, where the heteroaromaticradical can be substituted with further radicals R¹⁰, where R¹⁰ is anorganic radical with 1 to 10, in particular 1 to 6, carbon atoms, suchas, for example, C₁-C₄-alkyl, C₆-C₁₀-aryl, arylalkyl or alkylaryl with 1to 4 carbon atoms in the alkyl radical and 6 to 10, preferably 6, carbonatoms in the aryl radical, and two or more radicals R¹⁰ may be identicalor different.

Preferably, R¹ is a linear C₁-C₁₀-, in particular C₁-C₄-alkyl radical, abranched C₃-C₁₀-, in particular C₃-C₄-alkyl radical, a C₄-C₁₀-, inparticular C₅-C₈-cycloalkyl radical. Particularly preferably, R¹ is alinear C₁-C₁₀-, in particular C₁-C₄-alkyl radical.

The radical R² is hydrogen or an organic radical with 1 to 20 carbonatoms, such as, for example, C₁-C₂₀-alkyl, C₆-C₂₀-aryl, arylalkyl oralkylaryl with 1 to 10, preferably 1 to 4, carbon atoms in the alkylradical and 6 to 14, preferably 6 to 10, in particular 6, carbon atomsin the aryl radical, a saturated heterocyclic radical with 3 to 20carbon atoms or a heteroaromatic radical with 3 to 20 carbon atomshaving in each case at least one heteroatom selected from the groupconsisting of the elements N, P, O and S, in particular N, O and S,where the heteroaromatic radical can be substituted with furtherradicals R¹⁰.

Preferably, R² is a linear C₁-C₁₀-, in particular C₁-C₄-alkyl radical, abranched C₃-C₁₀-, in particular C₃-C₄-alkyl radical, a C₄-C₁₀-, inparticular C₅-C₈-cycloalkyl radical. Particularly preferably, R² is alinear C₁-C₁₀-, in particular C₁-C₄-alkyl radical.

Alternatively, the radicals R¹ and R², together with the atomsconnecting them, form a mono- or polycyclic, substituted orunsubstituted ring system with 3 to 20, preferably 5 to 14, carbonatoms, which can also comprise heteroatoms selected from the groupconsisting of the elements Si, N, P, O, and S. Preferably, the radicalsR¹ and R² are together a divalent group —(CH₂)_(x)—, where x is aninteger from 3 to 12, preferably 4 to 12, in particular 10.

The radical R³ is hydrogen or an organic radical having 1 to 20 carbonatoms, such as, for example, C₁-C₂₀-alkyl, C₆-C₂₀-aryl, arylalkyl oralkylaryl with 1 to 10, preferably 1 to 4, carbon atoms in the alkylradical and 6 to 14, preferably 6 to 10, in particular 6, carbon atomsin the aryl radical, a saturated heterocyclic radical with 3 to 20carbon atoms or a heteroaromatic radical with 3 to 20 carbon atomshaving in each case at least one heteroatom selected from the groupconsisting of the elements N, P, O and S, in particular N, O and S,where the heteroaromatic radical can be substituted with furtherradicals R¹⁰.

Preferably, R³ is hydrogen, a linear C₁-C₁₀-, in particular C₁-C₄-alkylradical, a branched C₃-C₁₀-, in particular C₃-C₄-alkyl radical, aC₄-C₁₀-, in particular C₅-C₈-cycloalkyl radical. Particularlypreferably, R³ is hydrogen or methyl.

The radical R⁴ is hydrogen or an organic radical with 1 to 20 carbonatoms, such as, for example, C₁-C₂₀-alkyl, C₆-C₂₀-aryl, arylalkyl oralkylaryl with 1 to 10, preferably 1 to 4, carbon atoms in the alkylradical and 6 to 14, preferably 6 to 10, in particular 6, carbon atomsin the aryl radical, a saturated heterocyclic radical with 3 to 20carbon atoms or a heteroaromatic radical with 3 to 20 carbon atomshaving in each case at least one heteroatom selected from the groupconsisting of the elements N, P, O and S, in particular N, O and S,where the heteroaromatic radical can be substituted with furtherradicals R¹⁰.

Preferably, R⁴ is hydrogen, a linear C₁-C₁₀-, in particular C₁-C₄-alkylradical, a branched C₃-C₁₀-, in particular C₃-C₄-alkyl radical, aC₄-C₁₀-, in particular C₅-C₈-cycloalkyl radical. R⁴ is particularlypreferably hydrogen or methyl.

The radical R⁵ is hydrogen or an organic radical with 1 to 20 carbonatoms, such as, for example, C₁-C₂₀-alkyl, C₆-C₂₀-aryl, arylalkyl oralkylaryl with 1 to 10, preferably 1 to 4, carbon atoms in the alkylradical and 6 to 14, preferably 6 to 10, in particular 6, carbon atomsin the aryl radical, a saturated heterocyclic radical with 3 to 20carbon atoms or a heteroaromatic radical with 3 to 20 carbon atomshaving in each case at least one heteroatom selected from the groupconsisting of the elements N, P, O and S, in particular N, O and S,where the heteroaromatic radical can be substituted with furtherradicals R¹⁰.

Preferably, R⁵ is hydrogen, a linear C₁-C₁₀-, in particular C₁-C₄-alkylradical, a branched C₃-C₁₀-, in particular C₃-C₄-alkyl radical, aC₄-C₁₀-, in particular C₅-C₈-cycloalkyl radical. R⁵ is particularlypreferably hydrogen or methyl.

The indice m is zero (0), one (1) or two (2). In the case of compoundsof the formula (I), m is preferably one (1) or two (2) and, in the caseof compounds of the formula (II), m is preferably zero (0) or one (1).Very particularly preferably, m is one (1) or two (2), in particular one(1).

The formation either of the cyclic enol ether of the formula (I) and/orof the formula (II) starting from a specific starting compound of theformula (III) depends decisively on which carbon atom of the double bondin the starting compound, either the radical R³ or the carbon atomcarrying the radicals R⁴ and R⁵, the more stable carbocation is formallyable to form through protonation of the double bond. For example, incases where m is 1, R³ is methyl and R⁴ and R⁵ are hydrogen, cyclic enolethers of the formula (I) are formed, and in cases where m is 1, R³ ishydrogen and R⁴ and R⁵ are methyl, cyclic enol ethers of the formula(II) are formed.

Preferably, in the process according to the invention, the indices inthe formula (I), (II) and (III) are defined as follows.

The radical R¹ is a C₁-C₁₀-, preferably C₁-C₄-alkyl radical, preferablya linear C₁-C₁₀-, preferably C₁-C₄-alkyl radical.

The radical R² is a C₁-C₁₀-, preferably C₁-C₄-alkyl radical, preferablya linear C₁-C₁₀-, preferably C₁-C₄-alkyl radical.

Alternatively, the radicals R¹ and R² are together a divalent group—(CH₂)_(x)—, where x is an integer from 3 to 12, preferably 4 to 12, inparticular 10.

The radical R³ is hydrogen or methyl.

The radical R⁴ is hydrogen or methyl.

The radical R⁵ is hydrogen or methyl.

The indice m is zero (0), one (1) or two (2). In the case of compoundsof the formula (I), m is preferably one (1) or two (2) and in the caseof compounds of the formula (II), m is preferably zero (0) or one (1).Very particularly preferably, m is one (1) or two (2), in particular one(1).

Preference is likewise given to a process according to the invention asdescribed previously, where the starting compound of the formula (III),which is a compound of the formula (IIIa) or a compound of the formula(IIIb),

is reacted to give the corresponding cyclic enol ether of the formula(IIa),

in which, in the formulae (IIa), (IIIa) and (IIIb)

-   n is zero (0) or one (1).

Particularly preferably, in compounds of the formula (IIIa), n is zero(0), which leads to the formation of the 5-membered cycloenol ether, andin compounds of the formulae (IIIb), n is 1, which leads to theformation of the 6-membered cycloenol ether.

The invention is illustrated by the following examples, although thesedo not limit the invention.

EXAMPLE 1

Allylation:

CDon (364.6 g), toluene (360 ml), tetrabutylammonium iodide (7.6 g) andsodium hydroxide solution (50% strength, 480 g) were introduced into thereactor and heated to 90° C. with stirring (400 rpm). At an internaltemperature of 90° C., the metered addition of allyl chloride (306.1 g)was started, during which the temperature in the reactor dropped andreflux started. Total metering time: 3 h. The two-phase reaction mixturewas then stirred overnight at 94° C. The reaction solution was thencooled to RT. At 65° C., 500 ml of water were added in order to dissolvethe accumulated solid in the aqueous phase. Following phase separation,the organic phase was washed twice with 500 ml of water. The organicphase was then also washed with 500 g of 10% strength sulfuric acid. Theaqueous phases were discarded in each case.

Cyclization:

213.5 g of allylation product are admixed with 5 ml of sulfuric acid ina distillation flask. In the distillation apparatus with 30 cm packedcolumn (3 mm metal Raschig rings) and Normag column head, a vacuum of 2mbar was applied, and 163.2 g of product were distilled off at a bottomtemperature of 138-142° C. (overhead temperature 108-115° C.).

EXAMPLE 2

Methallylcyclododecanone was prepared starting from CDon and methallylchloride, analogously as described in example 1 in the allylationsection.

Brønsted Acid Catalysis

In a 1000 ml three-neck flask with 30 cm Sulzer column and Normag columnhead, 1006 g of methallylcyclododecanone were introduced as initialcharge and admixed with 20 g of concentrated sulfuric acid. A vacuum of1 mbar was applied, the oil-bath temperature was increased to 140° C. Ata bottom temperature of 128-135° C., the bicycle was slowly distilledout of the reaction mixture (overhead temperature 91-96° C.). In total,866.35 g of product could be distilled out of the reaction mixture.

Lewis Acid Catalysis

In a 500 ml distillation flask with 30 cm packed column (3 mm wirerings) and Normag column head, 200 g of 2-(2-methallyl)cyclododecanonewere introduced as initial charge and admixed with 2 g of aluminumchloride. A vacuum of 2 mbar was applied, the oil-bath temperature wasslowly increased to 175° C. At a bottom temperature of 153-156° C., theproduct was distilled out of the reaction mixture (overhead temperature121-123° C.). In total, 140.5 g of product could be distilled out of thereaction mixture.

EXAMPLE 3

CDon (364.6 g), toluene (360 ml), tetrabutylammonium iodide (7.6 g) andsodium hydroxide solution (50% strength, 480 g) were introduced into thereactor and heated to 90° C. with stirring (400 rpm). At an internaltemperature of 90° C., the metered addition of1-chloro-3-methyl-2-butene (313.7 g) was started. The temperature washeld at 90° C. during the entire addition. Total metering time: 3 h. Thetwo-phase reaction mixture was after-stirred at 90° C. for 5 h. Thereaction solution was then cooled to RT. At 65° C., 500 ml of water wereadded in order to dissolve the accumulated solid in the aqueous phase.Following phase separation, the organic phase was washed twice with 500ml of water. The organic phase was then also washed with 500 g of 10%strength sulfuric acid. The aqueous phases were discarded in each case.

7 g of conc. sulfuric acid were added to 278 g of the intermediateproduct and then the solution was transferred to a 1 l distillationflask and distilled in a 70 cm packed column (3 mm metal Raschig rings)with reflux divided at a bottom temperature of 185° C., an overheadtemperature of 130-135° C., a pressure of 3 mbar and a reflux ratio of40:1 to 60:1. 191.7 g of the product could be distilled out of thereaction mixture.

EXAMPLE 4

2-Methallylcyclooctanone was prepared starting from cyclooctanone andmethallyl chloride, analogously as described in example 1 in theallylation section.

302.8 g of 2-methallylcyclooctanone were introduced as initial charge ina 1 l distillation flask with 30 cm packed column (3 mm wire rings),Normag column head and vacuum regulator. 3 g of concentrated sulfuricacid were added and a vacuum of 5 mbar was applied. The oil-bathtemperature was increased slowly to 130° C. At a bottom temperature of100-105° C., the bicycle formed was slowly distilled out of the reactionmixture. (Overhead temperature 77° C.). In total, 228.2 g of bicyclewith a purity of >96% could be obtained as fractions.

EXAMPLE 5

3-Methallyl-4-heptanone was prepared starting from 4-heptanone andmethallyl chloride, analogously as described in example 1 in theallylation section.

268 g of 3-methallyl-4-heptanone were introduced as initial charge in a1 l distillation flask with 30 cm packed column (3 mm wire rings),Normag column head and vacuum regulator, and admixed with 2.68 g ofconcentrated sulfuric acid. A vacuum of 20 mbar was applied and theoil-bath temperature was increased to 110° C. At a bottom temperature of83-88° C., the dihydro-furan formed was distilled out of the reactionmixture (overhead temperature 67-69° C.). In total, 208.1 g of productcould be obtained.

1-5. (canceled)
 6. A process for the preparation of cyclic enol ethersof the formulae (I) and/or (II)

which comprises cyclization of a starting compound of the formula (III)

in which m is zero (0), one (1) or two (2), R¹ is an organic radicalwith 1 to 20 carbon atoms, R² is hydrogen or an organic radical having 1to 20 carbon atoms, or the radicals R¹ and R², together with the atomsconnecting them, form a mono- or polycyclic, substituted orunsubstituted ring system with 3 to 20 carbon atoms which can alsocomprise heteroatoms selected from the group consisting of the elementsSi, N, P, O, and S, R³ is hydrogen or an organic radical with 1 to 20carbon atoms, R⁴ is hydrogen or an organic radical with 1 to 20 carbonatoms, and R⁵ is hydrogen or an organic radical with 1 to 20 carbonatoms. in the presence of a Brønstedt acid or Lewis acid, where thereaction is carried out as reactive distillation, where the formedcyclic enol ethers of the formulae (I) and/or (II) are separated offfrom the starting compound of the formula (III) by distillation from thereaction mixture.
 7. The process according to claim 6, where the molarratio of the Brönstedt acid or Lewis acid to the compound of the formula(III) is not greater than
 1. 8. The process according to claim 6, wherethe cyclization is carried out in the presence of a Brönstedt acid witha pKa value of less than
 5. 9. The process according to claim 6, inwhich, in the formulae (I), (II) and (III) m is zero (0), one (1) or two(2), R¹ is a C₁-C₁₀-alkyl radical, R² is a C₁-C₁₀-alkyl radical, or theradicals R¹ and R² together are a divalent group —(CH₂)_(x)—, where x isan integer from 3 to 12, R³ is hydrogen or methyl, R⁴ is hydrogen ormethyl, and R⁵ is hydrogen or methyl.
 10. The process according to claim8, in which, in the formulae (I), (II) and (III) R¹ is a C₁-C₁₀-alkylradical, R² is a C₁-C₁₀-alkyl radical, or the radicals R¹ and R²together are a divalent group —(CH₂)_(x)—, where x is an integer from 3to 12, R³ is hydrogen or methyl, R⁴ is hydrogen or methyl, and R⁵ ishydrogen or methyl.
 11. The process according to claim 6, where thestarting compound of the formula (III), which is a compound of theformula (IIIa) or a compound of the formula (IIIb),

is reacted to give the corresponding cyclic enol ether of the formula(IIa),

in which, in the formulae (IIa), (IIIa) and (IIIb) n is zero (0) or one(1).
 12. The process according to claim 10, where the starting compoundof the formula (III), which is a compound of the formula (IIIa) or acompound of the formula (IIIb),

is reacted to give the corresponding cyclic enol ether of the formula(IIa),

in which, in the formulae (IIa), (IIIa) and (IIIb) n is zero (0) or one(1).